In the period of the Level II award the applicant has developed an independent area of research focusing on the psychobiology and treatment of anxiety disorders. There are three main goals proposed for the next five years of research, each funded by separate project grants. First, I would like to continue to study the ventilatory physiology of patients with panic disorder and other anxiety disorders. This includes use of the carbon dioxide challenge approach, development of ambulatory respiratory monitoring, and exploration of cognitive factors that may influence respiratory findings in panic patients. Second, I will study the comparative efficacy of pharmacological and cognitive/behavioral therapies for patients with panic disorder, including attempting to establish patient characteristics that may predict differential treatment response. Third, I will use the model provided by the denervated heart of cardiac transplant patients to study basic mechanisms by which stress produces cardiovascular response. This work allows dissection of central and peripheral influences on the cardiovascular response to stressful and anxiogenic stimuli. In addition to these main projects, I propose to develop pilot projects in five additional areas: development of animal models of panic and separation anxiety, study of response to biological challenges in children with anxiety disorders, study the sympathetic and parasympathetic influences of heart rate variability in adults and children with anxiety disorder during a variety of laboratory challenges, studies of the efficacy and neurobiology of serotonin reuptake blocking medications in panic disorder, and an attempt to establish whether biological challenge tests can be useful in genetic studies of panic disorder.